Davallialactone protects against acetaminophen overdose-induced liver injuries in mice.

Abstract

Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Davallialactone (DAVA), a hispidin analog derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study evaluated whether DAVA plays protective roles against APAP hepatotoxicity in mice. Pretreatments with DAVA (10 mg/kg) prior to exposures of mice to a hepatotoxic dose of 600 mg/kg APAP significantly increased survival rate compared to APAP alone. To verify this effect, mice were treated with 400 mg/kg APAP 30 min after DAVA administration and were then sacrificed after 0.5, 1, 3, and 6 h. APAP alone caused severe liver injuries as characterized by increased plasma GOT and GPT levels, ATP and GSH depletion, and peroxynitrite and 4-HNE formations. These liver damages induced by APAP were significantly attenuated by DAVA pretreatments. The GSH/GSSG ratio nearly recovered to the levels observed in non-APAP-treated mice at 6h after APAP treatment in DAVA-pretreated mice. Furthermore, while hepatic ROS levels were increased by APAP exposures, pretreatments with DAVA completely blocked ROS formation. In addition, APAP-induced sustained activations of JNK and ERK were remarkably reduced by DAVA pretreatment. In conclusion, these results suggest that DAVA plays protective roles against APAP-mediated hepatotoxicity through function as ROS scavenger.

• Authors: Jung-Ran Noh, Yong-Hoon Kim, Jung Hwan Hwang, Gil-Tae Gang, Kyoung-Shim Kim, In-Kyoung Lee, Bong-Sik Yun, Chul-Ho Lee
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 58 Pg. 14-21 (Aug 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23583805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Lactones
• davallialactone
• Acetaminophen
• Adenosine Triphosphate
• Aspartate Aminotransferases
• Alanine Transaminase
• Glutathione

Topics

• Acetaminophen (poisoning)
• Adenosine Triphosphate (blood)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Chemical and Drug Induced Liver Injury (etiology)
• Drug Overdose (prevention & control)
• Glutathione (blood)
• Lactones (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Survival Rate